We propose to create a Transdisciplinary Tobacco Use Research Center (TTURC) for the study of the Bio-behavioral Basis of Tobacco Use. The purpose of the TTURC is to: (a) obtain a more complete understanding of the role of specific genetic factors and bio-behavioral mechanisms in tobacco use, in the context of psychological and social factors; and (b) apply this knowledge to the prevention, treatment, and reduction of harm from tobacco exposure. Consistent with the RFA, we have established a "virtual collaboratory" in the Washington, D.C./Maryland area, creating linkages among existing programs at the Georgetown University Medical Center (GUMC), NIH (intramural program), and University of Maryland. Since the RFA encourages collaboration with NIH intramural investigations, these collaborators will play a key role in all facets of the TTURC. The Specific Aims of the TTURC are: (1) To conduct three highly interrelated research projects aimed to identify the bio-behavioral basis of smoking initiation, smoking treatment, and harm from tobacco exposure. Specifically, all three projects: (a) investigate the role of specific dopamine genes in tobacco use; (b) explore the bio-behavioral mechanisms that link these genetic effects with tobacco use; and (c) evaluate the moderating effects of psychological, social, and/or demographic factors on tobacco use; (2) To create three specialized cores to serve the needs of these projects and the TTURC. These include: (a) an Administrative Core, (b) a Molecular Genetics Core, and (c) a Data Management Core; (c) To develop a program for research career development in the field of tobacco control. This program focuses on the selection, training, and mentoring of post-doctoral investigations and includes a multifaceted plan to reach female and minority candidates; and (4) To solicit and support a series of more focused high priority developmental research projects. These projects are chosen to extend the three primary research projects in both directions, to more basic research on nicotine addiction and to studies in health policy.